A neuronal mechanism underlying decision-making deficits during hyperdopaminergic states

Jeroen P H Verharen; Johannes W de Jong; Theresia J M Roelofs; Christiaan F M Huffels; Ruud van Zessen; Mieneke C M Luijendijk; Ralph Hamelink; Ingo Willuhn; Hanneke E M den Ouden; Geoffrey van der Plasse; Roger A H Adan; Louk J M J Vanderschuren

doi:10.1038/s41467-018-03087-1

A neuronal mechanism underlying decision-making deficits during hyperdopaminergic states

Jeroen P H Verharen, Johannes W de Jong, Theresia J M Roelofs, Christiaan F M Huffels, Ruud van Zessen, Mieneke C M Luijendijk, Ralph Hamelink, Ingo Willuhn, Hanneke E M den Ouden, Geoffrey van der Plasse, Roger A H Adan, Louk J M J Vanderschuren

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Hyperdopaminergic states in mental disorders are associated with disruptive deficits in decision making. However, the precise contribution of topographically distinct mesencephalic dopamine pathways to decision-making processes remains elusive. Here we show, using a multidisciplinary approach, how hyperactivity of ascending projections from the ventral tegmental area (VTA) contributes to impaired flexible decision making in rats. Activation of the VTA-nucleus accumbens pathway leads to insensitivity to loss and punishment due to impaired processing of negative reward prediction errors. In contrast, activation of the VTA-prefrontal cortex pathway promotes risky decision making without affecting the ability to choose the economically most beneficial option. Together, these findings show how malfunction of ascending VTA projections affects value-based decision making, suggesting a potential mechanism through which increased forebrain dopamine signaling leads to aberrant behavior, as is seen in substance abuse, mania, and after dopamine replacement therapy in Parkinson's disease.

Originele taal-2	Engels
Artikelnummer	731
Tijdschrift	Nature Communications
Volume	9
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1038/s41467-018-03087-1
Status	Gepubliceerd - 2018

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Verharen, J. P. H., de Jong, J. W., Roelofs, T. J. M., Huffels, C. F. M., van Zessen, R., Luijendijk, M. C. M., Hamelink, R., Willuhn, I., den Ouden, H. E. M., van der Plasse, G., Adan, R. A. H., & Vanderschuren, L. J. M. J. (2018). A neuronal mechanism underlying decision-making deficits during hyperdopaminergic states. Nature Communications, 9(1), Artikel 731. https://doi.org/10.1038/s41467-018-03087-1

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abstract = "Hyperdopaminergic states in mental disorders are associated with disruptive deficits in decision making. However, the precise contribution of topographically distinct mesencephalic dopamine pathways to decision-making processes remains elusive. Here we show, using a multidisciplinary approach, how hyperactivity of ascending projections from the ventral tegmental area (VTA) contributes to impaired flexible decision making in rats. Activation of the VTA-nucleus accumbens pathway leads to insensitivity to loss and punishment due to impaired processing of negative reward prediction errors. In contrast, activation of the VTA-prefrontal cortex pathway promotes risky decision making without affecting the ability to choose the economically most beneficial option. Together, these findings show how malfunction of ascending VTA projections affects value-based decision making, suggesting a potential mechanism through which increased forebrain dopamine signaling leads to aberrant behavior, as is seen in substance abuse, mania, and after dopamine replacement therapy in Parkinson's disease.",

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AU - Verharen, Jeroen P H

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AU - van Zessen, Ruud

AU - Luijendijk, Mieneke C M

AU - Hamelink, Ralph

AU - Willuhn, Ingo

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AU - Adan, Roger A H

AU - Vanderschuren, Louk J M J

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AB - Hyperdopaminergic states in mental disorders are associated with disruptive deficits in decision making. However, the precise contribution of topographically distinct mesencephalic dopamine pathways to decision-making processes remains elusive. Here we show, using a multidisciplinary approach, how hyperactivity of ascending projections from the ventral tegmental area (VTA) contributes to impaired flexible decision making in rats. Activation of the VTA-nucleus accumbens pathway leads to insensitivity to loss and punishment due to impaired processing of negative reward prediction errors. In contrast, activation of the VTA-prefrontal cortex pathway promotes risky decision making without affecting the ability to choose the economically most beneficial option. Together, these findings show how malfunction of ascending VTA projections affects value-based decision making, suggesting a potential mechanism through which increased forebrain dopamine signaling leads to aberrant behavior, as is seen in substance abuse, mania, and after dopamine replacement therapy in Parkinson's disease.

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A neuronal mechanism underlying decision-making deficits during hyperdopaminergic states

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